Table 2.

Comparison chart of ctDNA, Tissue Assay, and CTCs

Metrics	ctDNA	Tissue Assay	Circulating Tumor Cells
Risks	Minimally invasive test Blood draw risks	Invasive test Biopsy risks	Minimally invasive test Blood draw risks
Factors that affect role as a tumor marker	Global sample of tumors Well suited to capture intratumor genetic heterogeneity Variability of ctDNA amount is dependent on cfDNA in sample, which can make it difficult to obtain enough sample, issues with minimal allele frequency required to detect, false positive and false negative tests	Regional sample of tumor based on location of biopsy site mean that heterogeneity within the tumor itself may be missed	Global sample of tumor Well suited to capture intratumor genetic heterogeneity Very low concentrations in blood leading to low capture rates Misses low-EpCAM CTC populations if based on affinity marker testing. Issues with potential low purity if isolated based on size or negative selection.
Role as a screening test	Currently being studied as a screening test for multiple cancers.	Current practice for diagnosis of a cancer type. Not a screening test.	Not cost effective as a screening test currently. Not all cancer patients have detectable CTCs.
Selecting targeted therapy	If targets are known or prevalent, ddPCR or targeted panels for ctDNA may be favorable	Evidence exists for treatment selection based on tissue biopsy results in early and advanced cancers	If potentially actionable treatment targets are unknown, CTCs may be preferable to discover the full spectrum of available targeted therapy options
Advantages in monitoring therapy effectiveness	Possible ability to gather temporal data on tumor heterogeneity throughout treatment, but no evidence of clinical validity. More studies needed.	More difficult to re-biopsy to show evolution of metastases or response to treatment	Possible ability to gather temporal data on tumor heterogeneity throughout treatment. However, more studies and research needed.
Clinical Utility	Limited evidence of clinical utility for treatment selection, and no evidence for other uses	Evidence of utility in treatment selection for early and advanced cancers	Limited evidence of clinical utility for treatment selection
Clinical Validity	Insufficient evidence for most assays.	Current standard practice for treatment selection for early and advanced cancers.	Insufficient evidence for most assays.

ctDNA: circulating tumor DNA

CTC: circulating tumor cells